Monoamine oxidase (MAO) is an important degradative enzyme in the monoamine neural tracts whose role in psychiatric disease has been the subject of prolonged controversy. The pharmacologic action of MAO inhibitors has been examined in many past studies. Recently, considerable attention has been directed to the mechanism(s) by which other psychotropic drugs affect MAO, since neuroleptic drugs have been reported in several studies to alter platelet MAO activities in psychiatric patients. This proposal focuses on the origins of the functional difference between the two forms of the enzyme (MAO A and B), which oxidize monoamine neurotransmitters with varying efficiencies and respond differently to inhibitory drugs and hormones. We propose to adapt methodologies which have been applied with success in basic studies of cell systems to examine the endogenous and exogenous factors which control levels of MAO A and B activity and concentration in human tissues. The effects of drugs and hormones on in vivo and in vitro MAO synthetic systems will be examined in the light of genetic controls on protein structure and synthesis and mechanisms which regulate the expression of MAO A and B genes in human cells.